多囊卵巢综合征病因学文献研究及情志致病病因探讨

【作者】 王燕；

【导师】 李光荣；

【作者基本信息】 中国中医科学院 ， 中医妇科， 2009， 博士

【摘要】 多囊卵巢综合征（Polycystic ovarian syndrome，PCOS）是现代妇科临床中最常见的内分泌紊乱性疾病，与其相伴随发生的肥胖、高胰岛素血症、糖脂质代谢紊乱、Ⅱ型糖尿病、心血管疾病等严重影响着女性健康。PCOS病因仍不十分明确。目前认为，PCOS是多种因素共同作用的结果。导师李光荣教授从事中医妇科临床40余年，在中医药治疗PCOS方面积累了丰富的经验，提出“情志不遂是PCOS重要发病因素之一”的学术思想。以补肾调肝法治疗PCOS，疗效显著。本论文是关于PCOS病因学的研究。旨在主要通过文献研究，初步总结中西医关于PCOS病因学的认识和研究成果，从理论方面探讨情志不遂引起PCOS的可能发病机制，并通过以补肾调肝法治疗PCOS的临床研究反证情志不遂对PCOS发病的重要影响。1文献研究1．1古代文献中关于多囊卵巢综合征类似病症的病因病机研究“多囊卵巢综合征”是现代医学病名，其相关病症的记载在古代医籍中散见于“崩漏”、“月经后期”、“闭经”、“不孕”等章节中。古代医籍对疾病的描述中具备“月经不调（崩漏、月经后期或闭经）、不孕、肥胖”其中两项者则认为是类似多囊卵巢综合征的病症。古代医籍的检索依托《中华医典》。1．1．1古代医籍研究显示，劳伤气血和七情内扰在多囊卵巢综合征相关病症“不孕、崩漏、闭经或月经后期”的致病中占据重要地位，尤其在月经不调—崩漏、闭经或月经后期的致病中更为重要；在不孕的致病因素中，劳伤气血和痰湿为患是两个主要因素，痰湿不孕表现在肥胖不孕中。同时，脏气不足，尤其是脾肾不足也是重要的致病因素。1．1．2总结类似多囊卵巢综合征病症的相关病因：脏气不足、劳伤气虚、七情内扰和痰湿为四类主要病因，其中痰湿病因高居首位，其因在于：古籍中将肥胖形体归为痰湿病因，而肥胖为类似多囊卵巢综合征病症入选条件之一，使肥胖患者入选多囊卵巢综合征类似病症的机率增加；同时说明古代医家已经重视到痰湿因素在不孕及闭经或月经后期中的致病作用。1．2现代中医文献病因病机研究现代中医文献检索以“多囊卵巢综合征”为检索主题词，检索年限1988．1—2008．12。病因病机归纳显示：PCOS脏腑辨证以肾、肝、脾三脏为主，病理产物涉及痰湿、痰瘀、瘀血。辨证分型频率超过5％的为前六项证型依次是：肾虚痰瘀，肾虚血瘀，肾虚，肾虚痰湿，脾肾阳虚、痰瘀互阻，肾虚肝郁。其中，肾虚是公认的PCOS最主要的病因病机，肾虚合并痰、湿、瘀是相关主要证候。1．3 PCOS病因学现代文献研究成果目前关于PCOS病因学学说主要有：①遗传学说；②胰岛素抵抗；③下丘脑—垂体—性腺轴异常；④青春期发育亢进学说；⑤肾上腺功能初现亢进学说。其他发病影响因素还有：环境因素、饮食因素、慢性炎症学说、精神心理因素、药物影响。2理论研究2．1情志不遂，肝气不舒是女性“月经不调、不孕”的重要致病因素，也多囊卵巢综合征的重要病因病机。2．2精神心理因素可以影响女性生殖内分泌功能。PCOS以闭经和月经不调、不孕为主要临床症状，心理应激状态时出现的神经递质改变和细胞因子变化很多与PCOS的病理生理改变有类似之处。因此，心理应激很可能是PCOS重要的诱发因素之一。2．3“肾虚是多囊卵巢综合征情志致病之基础，情志不遂是PCOS重要的发病因素之一”是导师李光荣教授对PCOS辨证治疗的学术思想。对情志不遂致病作用的强调是导师学术思想的特色。因此导师以补肾调肝法治疗多囊卵巢综合征，“重视调畅情志”贯穿治疗始终。3临床研究“情志不遂是多囊卵巢综合征重要的发病因素之一”是导师李光荣教授认识PCOS的主要学术思想。以补肾调肝法前瞻性治疗PCOS患者42例，其目的在于证明导师学术思想的正确性。研究采用自身前后对照法。总结疗效：①PCOS患者疗后排卵率63．63％，妊娠成功率72．72％。②治疗后患者月经周期缩短，经期缩短，均具有统计学意义。③疗后患者LH、LH／FSH、T下降，E₂水平升高，均具有统计学意义。说明补肾调肝法是治疗PCOS的正确疗法，同时进一步说明情志不遂是PCOS发生发展的重要影响因素。4结论4．1文献研究：①古代文献中论及多囊卵巢综合征类似病症的主要病因为：脏气不足、劳伤气虚、七情内扰和痰湿。②现代中医文献论及PCOS主要病因为肾虚，肾虚合并痰、湿、瘀是相关主要证候。③PCOS病因学现代文献研究主要学说有：遗传学说；胰岛素抵抗；下丘脑—垂体—性腺轴异常；青春期发育亢进学说；肾上腺功能初现亢进学说。其他发病影响因素还有：环境因素、饮食因素、慢性炎症学说、精神心理因素、药物影响。4．2理论研究：肾虚是多囊卵巢综合征情志致病之基础，情志不遂是PCOS重要的发病因素之一。4．3临床研究证明补肾调肝、强调调节情志是治疗PCOS的有效治则，说明情志不遂是PCOS发生发展的重要影响因素。更多还原

【Abstract】 Polycystic ovarian syndrome（PCOS）is one of the most common endocrinedisorders in modern gynecological clinical practice.The accompanyingdiseases and disorders such as obesity,hyperinsulinemia,glucose andlipid metabolic disturbance,type 2 diabetes and cardiovascular diseasesare seriously affect the women health.The PCOS etiology remains unknownand is believed that it is a result of many pathogenic factors at present.My tutor,Prof.Li Guangrong,practicing Traditional Chinese Medicine（TCM）gynecology over 40 years,believes that“emotional disturbance”is one of the leading causes of PCOS.With kidney-nourishing andliver-adjusting therapies,she has obtained significant therapeuticresult and accumulated rich experience in the treatment of PCOS.This paper was a study on PCOS etiology.Through literature research,we summarized the previous achievements on PCOS etiology both in TCM andconventional medicine and explored the possible pathogenesis caused byemotional disturbance in theory.By treating PCOS with kidney-nourishingand liver-adjusting therapies in the clinical practice,we also provedthe important influence of emotional disturbance to the PCOS.1 Literature research1.1 Etiology and pathogenesis of symptoms similar to PCOS in ancientliteraturePCOS is a disease name in conventional medicine.Its related symptomswere written in the chapters like“uterine bleeding”,“delayed menstrualcycle”,“amenorrhea”and“infertility”in ancient literature.Thedisease was identified as symptom similar to PCOS if it possessed two offollowing---“irregular menstruation including uterine bleeding,delayedmenstrual cycle or amenorrhea”,“infertility”and“obesity”in ancientliterature.Ancient literatures included in Zhonghuayidian wereretrieved. 1.1.1 The ancient literature showed that overstrain resulting in Qi andblood impairment and emotional disturbance were main causes of symptomsthat related to PCOS,for example,infertility,uterine bleeding,amenorrhea and delayed menstrual cycle,and they were more importantcauses of irregular menstruation such as uterine bleeding,amenorrhea anddelayed menstrual cycle.Overstrain resulting in Qi and blood impairmentand phlegm-dampness were the main causes of infertility.The infertilitycaused by phlegm-dampness could be found accompanied with symptom ofobesity.Deficiency of Zang Qi,especially deficiency of spleen and kidneyQi,was another important cause of infertility.1.1.2 A summary to the etiology of symptoms similar to PCOSDeficiency of Zang Qi,overstrain resulting in Qi deficiency,emotional disturbance and phlegm-dampness were four types of causes ofsymptoms similar to PCOS.Among them,phlegm-dampness was major onebecause,in ancient literature,phlegm-dampness was a cause of obesityand obesity was one of inclusion criteria of symptoms similar to PCOS,which increased the possibility of obesity patients be included in thegroup of symptoms similar to PCOS.These also suggested that ancient TCMdoctors had noticed the pathogenic role of phlegm-dampness in infertility,amenorrhea and delayed menstrual cycle.1.2 Etiology and pathogenesis in modern TCM literaturePCOS,as a key word,was retrieved in Modern TCM literature fromJan.1988 to Dec.2008.The results showed that three organs,kidney,liverand spleen were mainly involved in Zang and Fu differentiation.Pathogenicproducts were phlegm-dampness,phlegm stagnation and blood stasis.Thetop six differentiation types with the appearance frequency over 5% werekidney deficiency combined with phlegm stagnation,kidney deficiencycombined with blood stasis,kidney deficiency,kidney deficiency combinedwith phlegm-dampness,spleen and kidney yang deficiency,phlegm and blood stasis blocking and kidney deficiency combined with liver depressionrespectively.Among them,kidney deficiency was recognized as a leadingetiology and pathogenesis of PCOS.Kidney deficiency combined withphlegm-dampness and blood stases were main differentiation types of PCOS.1.3 PCOS etiology in modern literatureThe main PCOS etiology theories included heredity,insulin resistance,hypothalamus-pituitary-sexual gland axis abnormal,puberty overdevelopment and adrenarche hyperfunction.Some other pathogenic factorswere environment,diet,chronic inflammation,psychological factor andmedicine.2.Theory research2.1 Emotion disturbance and liver Qi depression are the pathogenic factorsof irregular menstruation and infertility and also the important etiologyand pathogenesis of PCOS.2.2 Spirit and psychological factors could affect female reproductive andendocrine functions.Amenorrhea,irregular menstruation and infertilityare main clinical symptoms of PCOS.Under the psychological stress state,the alterations of neurotransmitter and cell factor are similar to thepathological and physiological changes of PCOS.Therefore,psychologicalstress is probably one of the important inducements.2.3 Kidney deficiency is the basis of PCOS introduced by emotionaldisturbance and emotional disturbance is an important inducement of PCOS,which are academic thoughts of my tutor,Prof.Li Guangrong,in PCOStreatment.Highlighting the pathogenic function of emotional disturbanceis the characteristic of Prof.Li’ s academic thoughts.Therefore,sheapplies kidney-nourishing and liver-adjusting therapies and,at same time,soothes the emotion in the whole process of PCOS treatment.3 Clinical studyEmotional disturbance is an important inducement of PCOS,which is an academic thought of Prof.Li Guangrong in PCOS treatment.The aim thatwe prospectively treated 42 PCOS cases with kidney-nourishing andliver-adjusting therapies was to proof the validity of Prof.Li’s academicthought.Before and after self control study was adoptedResults:①POCS infertility patients’ ovulation rate was 63.63% and success rateof pregnancy was 72.72% after treatment.②After treatment both menstrual cycle and menstrual period were shortedwith statistic significance.③After treatment,LH,LH/FSH and T levels decreased and E₂ level increasedwith statistic significance,which indicated that kidney-nourishing andliver-adjusting were appropriate therapies for POCS treatment andemotional disturbance was an important factor in the development of POCS.4 Conclusion4.1 Literature research:①In ancient literature,it showed that the main etiology of symptomssimilar to PCOS were deficiency of Zang Qi,overstrain resulting in Qideficiency,emotional disturbance and phlegm-dampness.②Modern TCM literature suggested that kidney deficiency was a mainetiology of PCOS.Kidney deficiency combined with phlegm-dampness andblood stases were main differentiation types of PCOS.③The main modern PCOS etiology theories included heredity,insulinresistance,hypothalamus-pituitary-sexual gland axis abnormal,pubertyover development and adrenarche hyperfunction.Some other pathogenicfactors were environment,diet,chronic inflammation,psychologicalfactor and medicine.4.2 Theory research:Kidney deficiency is the basis of PCOS introduced by emotional disturbance and emotional disturbance is an important inducement of PCOS.4.3 Clinical studies indicated that therapies of kidney-nourishing,liver-adjusting and highlighting soothing emotion were effectivetreatment for POCS and emotional disturbance was an important factor inthe development of POCS.更多还原